An environmental risk assessment for losses to wastewater from galenical manufacturing at solid medicinal products at F. Hoffmann-La Roche in Basle, Switzerland, was performed based on an annual total materials balance. This balance resulted in a loss factor of 0.2% relative to the sum of all starting materials, which was later confirmed as valid by analysis for 1 specific active pharmaceutical ingredient (API). The initial risk assessment for all 25 different APIs formulated resulted in no evident risk for the wastewater treatment plant, based on biodegradation no-effect data. However, based on acute ecotoxicity data, potential risk to the local receiving water, the River Rhine, was identified from 1 single API, the antibiotic sulfamethoxazole (SMX). A refinement of the risk assessment for SMX, based on chronic ecotoxicity data, or the predicted no-effect concentration (PNEC), and documented sewage works degradability, or the predicted environmental concentration (PEC), led to a significant decrease of the initial PEC/PNEC ratio to well below 1. In view of this refinement, the final conclusion is that the galenical production investigated poses no significant risk to the environment.

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The switch of activated B cells to IgE synthesis is an interleukin (IL)-3-dependent process. It is currently thought that specific T cells activated by antigen presented in the context of class II major histocompatibility complex are the major source of IL-4. Recently it has been demonstrated that a splenic non-T non-B cell population (termed NBNT) has the capacity to produce IL-4 following IgE and IgG receptor cross-linkage. In this study we demonstrate that IL-4 producing NBNT cells can induce the switch of lipopolysaccharide-activated B cells to the synthesis of IgG1 and IgE antibodies. Furthermore, it was found that not only IgE receptor cross-linkage but IL-3 was able to stimulate NBNT cells to produce IL-4 and induce the switch of B cells to IgE synthesis. NBNT cells derived from the spleen and bone marrow of SCID mice were able to produce IL-4 on exposure to IL-3. This suggested that the ability of IL-3 to stimulate IL-4 production was not dependent on prior exposure of the NBNT cells to antibody complexes in vivo. Taken together these findings represent the first observation that enough IL-4 is produced by NBNT cells to actually influence a B cell IgG/Ig response. The findings also clearly demonstrate that B cells do not need high concentrations of IL-4 to be directed to switch to IgG1 and IgE synthesis.

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